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The aim of the experiment was to evaluate the potential of promising summer maize genotypes and optimal stage of harvesting these genotypes for ensiling in terms of dry matter (DM), starch, and crude protein (CP) yields, silage fermentation quality, nutrients profile, total digestible nutrients, metabolizable energy (ME) content, Cornell Net Carbohydrate and Protein System (CNCPS) carbohydrate (CHO) subfractions composition, in vitro DM digestibility (DMD) and in situ starch degradation characteristics. Six maize genotypes were chosen for the study: DK9108 from Monsanto, P30Y87, P3939 from Pioneer, QPM-300 (quality protein maize) and W94 from the International Maize and Wheat Improvement Center (CIMMYT), and a local cultivar, Afgoii, from the Cereal Research Institute (Persabaq, KP). A total of 72 plots (8 m × 10 m) were blocked in three replicate fields, and within each field, each genotype was sown in four replicate plots according to a randomized complete block design. For the data analysis, the Proc-Mixed procedure of Statistical Analysis System with repeated measure analysis of variance was used. The DM yield was strongly influenced (P < 0.001) by maize genotypes, varying from 12.6 to 17.0 tons/ha. Except for total CHO and ammonia nitrogen (NH3-N), the contents of all measured chemical components varied (P < 0.001) among the genotypes. Further comparison revealed that, genotype P3939 had a higher (P < 0.05) content of CP (7.27 vs. 6.92%), starch (36.7 vs. 27.9%), DMD (65.4 vs. 60.0%), ME (2.51 vs. 2.30 Mcal/kg) and lactic acid (5.32 vs. 4.83%) and lowest content of NDF (37.3 vs. 43.1%), pH (3.7 vs. 4.10) compared to the local cultivar (Afgoii). Advancement of post-flowering maturity from 25 to 35% DM (23 to 41 days after flowering (DAF)) increased (P < 0.05) the DM yield (10.4 to 17.8 tons/ha), starch content (29.1 to 35.0%), DMD (65.3 to 67.3%) and ME (2.34 to 2.47 Mcal/kg), and decreased (P < 0.001) the contents of CP (7.42-6.73%), NDF (48.8-38.5%), pH (4.10 to 3.60), NH3-N (8.93-7.80%N) and effective degradability of starch (95.4 to 89.4). Results showed that for higher yields and silage nutritional and fermentation quality, maize crops should be harvested at whole crop DM content of 30-35% (34 to 41 DAF). It was further concluded that genotype P3939 is the most suitable summer maize genotype for silage production in terms of yields and silage nutritional and fermentation quality under the hot environmental conditions of the tropics.
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Ensilaje , Zea mays , Zea mays/genética , Genotipo , Clima Tropical , Fermentación , Almidón , Carbohidratos , Proteínas de Plantas , Pakistán , AgriculturaRESUMEN
This study investigates the differential responses of two maize genotypes, SC180 and SC168, to salt stress, aiming to elucidate the mechanisms underlying salinity tolerance and identify traits associated with improved stress resilience. Salinity stress, imposed by 150 mM NaCl, adversely affected various growth parameters in both genotypes. SC180 exhibited a more pronounced reduction in shoot length (13.6%) and root length (13.6%) compared to SC168, which showed minimal reductions (3.0% and 2.3%, respectively). Additionally, dry weight losses in SC180's leaves, stems, and roots were significantly greater than those in SC168. Under salinity stress, both genotypes accumulated Na+ in all organs, with SC168 showing higher Na + concentrations. However, K+ levels decreased more significantly in SC180's leaves than in SC168's. The study also assessed physiological responses, noting that SC180 experienced a substantial reduction in relative water content (RWC) in leaves (22.7%), while SC168's RWC remained relatively stable (5.15%). Proline accumulation, a marker for osmotic adjustment, increased 2.3-fold in SC168 compared onefold in SC180. Oxidative stress indicators, such as electrolyte leakage and hydrogen peroxide levels, were elevated in both genotypes under salt stress, with SC180 showing higher increases (48.5% and 48.7%, respectively) than SC168 (35.25% and 22.0%). Moreover, antioxidant enzymes (APX, CAT, POD, SOD, GR) activities were significantly enhanced in SC168 under salinity stress, whereas SC180 showed no significant changes in these activities. Stress indices, used to quantify and compare salinity tolerance, consistently ranked SC168 as more tolerant (average rank = 1.08) compared to SC180 (average rank = 1.92). Correlation analyses further confirmed that SC168's superior tolerance was associated with better Na + regulation, maintenance of K+ levels, and a robust antioxidant defense system. In conclusion, SC168 demonstrated greater resilience to salinity stress, attributed to its efficient ion regulation, stable water status, enhanced osmotic adjustment, and strong antioxidant response. These findings provide valuable insights for breeding and developing salinity-tolerant maize varieties.
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Antioxidantes , Genotipo , Tolerancia a la Sal , Zea mays , Zea mays/genética , Zea mays/fisiología , Zea mays/crecimiento & desarrollo , Zea mays/metabolismo , Antioxidantes/metabolismo , Tolerancia a la Sal/genética , Sodio/metabolismo , Estrés Oxidativo , Hojas de la Planta/fisiología , Hojas de la Planta/metabolismo , Hojas de la Planta/genética , Hojas de la Planta/crecimiento & desarrollo , Potasio/metabolismoRESUMEN
Many studies have been conducted on the use of ultra-small iron oxide nanoparticles (USIONs) (d < 3 nm) as potential positive magnetic resonance imaging (MRI)-contrast agents (CAs); however, there is dearth of research on clustered USIONs. In this study, nearly monodispersed clustered USIONs were synthesized using a simple two-step one-pot polyol method. First, USIONs (d = 2.7 nm) were synthesized, and clustered USIONs (d = 27.9 nm) were subsequently synthesized through multiple cross-linking of USIONs with poly(acrylic acid-co-maleic acid) (PAAMA) polymers with many -COOH groups. The clustered PAAMA-USIONs exhibited very weak ferromagnetism owing to the magnetic interaction between superparamagnetic USIONs; this was evidenced by their appreciable r1= 3.9 sâ1mMâ1and high r2/r1ratio of 14.6. Their ability to function as a dual-modal T1/T2MRI-CA in T1-weighted MRI was demonstrated when they simultaneously exhibited positive and negative contrasts in T1-weighted MRI of tumor model mice after intravenous injection. They displayed positive contrasts at the kidneys, bladder, heart, and aorta and negative contrasts at the liver and tumor. .
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Preterm birth is one of the leading causes of death in the perinatal period, this study was conducted to investigate the predictive value of ß-HCG Levels in cervicovaginal secretions and maternal risk factors in preterm delivery. This cross-sectional study was conducted over a six-month period from January 1 to June 30, 2021, in Baghdad hospitals. The data were collected and used from the mothers who went to the hospital for delivery. Demographic information of patients and some risk factors were investigated. Vaginal secretions were sampled with a cotton swab. ß-HCG level in weeks 29, 31, 33, and 35 was measured by ELISA method. Data were analyzed with SPSS Ver 25 software and a significance level of less than 0.05 was considered. The mean age of the study participants was 28.29 ± 5.68 years. There was a significant difference in the level of ß-HCG between women with full-term delivery and pre-term women in weeks 29, 31, 33, and 35 of pregnancy (P ≤ 0.001). Maternal factors such as age older than 35 years, BMI, history of thyroid disease, blood pressure, premature rupture of the amniotic sac, parity, twin and multiple births, and decreased amniotic fluid volume have been identified as factors affecting preterm delivery. The ß-HCG level can also be a helpful marker for preterm birth.
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Nacimiento Prematuro , Embarazo , Humanos , Femenino , Recién Nacido , Adulto Joven , Adulto , Pronóstico , Estudios Transversales , Factores de RiesgoRESUMEN
Nanoparticles (NPs) exhibit fascinating size-dependent chemical and physical characteristics that make them useful for a variety of applications. The present paper reports the green synthesis of CuO NPs and B-doped CuO NPs (B-CuO NPs) from Livistona chinensis leaf extract. Not much work has been reported on the use of the plant extract for the fabrication of NPs, particularly those of Cu and its doped counterparts. Various spectroscopic techniques were used to characterize the synthesized NPs. In the FT-IR spectra, peaks obtained at 504 cm-1 to 600 cm-1 were due to Cu-O vibrations. The energy dispersive X-ray analysis (EDX) spectra confirmed the CuO NPs' composition and B's presence inside the NPs. The peak pattern in X-ray diffraction (XRD) spectrum confirmed the crystalline and monoclinic phases of the NPs. The average crystalline size of CuO NPs and B-CuO NPs was 19.56 nm and 17.30 nm respectively. The CuO and B-CuO NPs were tested against three Gram-positive bacterial strains namely Bacillus subtilis, Micrococcus luteus, and Staphylococcus aureus and three Gram-negative Escherichia coli, Salmonella abony, and Pseudomonas aeruginosa through Agar well diffusion method and it was found that CuO NPs showed higher activity than B-CuO NPs.
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A new class of thiophene-based molecules of 5-bromothiophene-2-carboxylic acid (1) have been synthesized in current research work. All analogs 4A-4G were synthesized with optimized conditions by coupling reactions of 2-ethylhexyl 5-bromothiophene-2-carboxylate (3) with various arylboronic acids. The results indicated that the majority of compounds showed promising effective in vitro antibacterial activity. Herein, 2-ethylhexyl-5-(p-tolyl)thiophene-2-carboxylate (4F), in particular among the synthesized analogs, showed outstanding antibacterial action (MIC value 3.125 mg/mL) against XDR Salmonella Typhi compared to ciprofloxacin and ceftriaxone. The intermolecular interaction was investigated by using a molecular docking study of thiophene derivatives 4A-4G against XDR S. Typhi. The values of the binding affinity of functionalized thiophene molecules and ciprofloxacin were compared against bacterial enzyme PDB ID: 5ztj. Therefore, 4F appears to be a promising antibacterial agent and showed the highest potential value. Density functional theory (DFT) calculations were executed to examine the electronic, structural, and spectroscopic features of the newly synthesized molecules 4A-4G.
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Antibacterianos , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Salmonella typhi , Tiofenos , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Salmonella typhi/efectos de los fármacos , Tiofenos/química , Tiofenos/farmacología , Tiofenos/síntesis química , Teoría Funcional de la Densidad , Ácidos Carboxílicos/química , Ácidos Carboxílicos/farmacología , Estructura Molecular , Relación Estructura-Actividad , Ciprofloxacina/farmacología , Ciprofloxacina/químicaRESUMEN
Wound healing is a complex physiological process involving coordinated cellular and molecular events aimed at restoring tissue integrity. Acute wounds typically progress through the sequential phases of hemostasis, inflammation, proliferation, and remodeling, while chronic wounds, such as venous leg ulcers and diabetic foot ulcers, often exhibit prolonged inflammation and impaired healing. Traditional wound dressings, while widely used, have limitations such poor moisture retention and biocompatibility. To address these challenges and improve patient outcomes, scaffold-mediated delivery systems have emerged as innovative approaches. They offer advantages in creating a conducive environment for wound healing by facilitating controlled and localized drug delivery. The manuscript explores scaffold-mediated delivery systems for wound healing applications, detailing the use of natural and synthetic polymers in scaffold fabrication. Additionally, various fabrication techniques are discussed for their potential in creating scaffolds with controlled drug release kinetics. Through a synthesis of experimental findings and current literature, this manuscript elucidates the promising potential of scaffold-mediated drug delivery in improving therapeutic outcomes and advancing wound care practices.
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Sistemas de Liberación de Medicamentos , Polímeros , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Humanos , Sistemas de Liberación de Medicamentos/métodos , Polímeros/química , Animales , Andamios del Tejido/química , Liberación de Fármacos , VendajesRESUMEN
OBJECTIVES: The contribution of pancreatic secretions in iron metabolism has been elucidated, but the clinical outcomes of iron deficiency on pancreatic function are debatable. This study aimed to investigate the modulation of euglycemic endocrine and exocrine pancreatic excretions in response to variations in iron availability. SUBJECTS AND METHODS: Serum levels of insulin, glucagon, insulin-to-glucagon ratio (IGR), and amylase were determined in 170 adult subjects with variable levels of serum iron. RESULTS: Control (n = 46) and iron-deficient (n = 124) subjects had significant differences (p < 0.001) in their average levels of insulin (68.7 ± 0.5 vs. 100.0 ± 2.0 pmol/dL), glucagon (17.9 ± 0.6 vs. 10.8 ± 0.8 pmol/dL), IGR (4.0 ± 0.1 vs. 19.5 ± 2.1), and amylase (29.7 ± 0.9 vs. 17.5 ± 0.2). The upregulation of serum insulin levels increases proportionally and gradually to the extent of iron deficiency as compared to an abrupt downregulation of serum levels of glucagon and amylase. A significant association was observed between serum iron and IGR (r = -0.645, p < 0.001) and amylase levels (r = 0.653, p < 0.001). The receiver operating characteristic curve analysis defines an excellent predictivity of the reduced serum iron level to discriminate subjects with upregulated IGR and amylase levels with area under curves of 0.938 and 0.905, respectively. CONCLUSION: Iron deficiency is associated with an adaptive modulation of euglycemic endocrine and exocrine secretions that is consistent with a status of insulin resistance.
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Amilasas , Glucagón , Insulina , Deficiencias de Hierro , Humanos , Glucagón/sangre , Masculino , Femenino , Adulto , Amilasas/sangre , Insulina/sangre , Persona de Mediana Edad , Hierro/sangre , Hierro/metabolismo , Páncreas Exocrino/metabolismo , Anemia Ferropénica/sangre , Glucemia/análisis , Adulto JovenRESUMEN
Background: Apolipoprotein E (APOE) gene polymorphism has been implicated in the pathogenesis of various metabolic disorders, including type 2 diabetes mellitus (T2DM). Type 2 diabetes mellitus (T2DM) is a major public health concern worldwide, including in Pakistan. Cardiovascular problems linked with T2DM have a significant impact on individuals and society. The goal of this study is to investigate the relationship between Apolipoprotein E (ApoE) genotypes, dyslipidemia, and cardiovascular complications such as ischemic heart disease (IHD) and stroke. Methods: This study was carried out on 260 subjects divided into controls and diabetics. The diabetics were further divided into four subgroups such as D1: diabetics without cardiovascular issues, D2: diabetics with heart disease, D3: diabetics with stroke, and D4: diabetics with both heart disease and stroke. Anthropometric parameters (age, BMI) and risk factors (smoking, diabetes duration, hypertension) were assessed in all groups. Serum levels of TC, TG, LDL, HDL, VLDL, creatinine, BSF, and HbA1c were also measured. Apolipoprotein E gene polymorphism was determined using PCR-RFLP. Results: Hypertension, BMI, and dyslipidemia are defined as elevated levels of total cholesterol, triglycerides, LDL, and VLDL, and decreased levels of HDL. Uncontrolled hyperglycemia (elevated fasting blood sugar and glycated hemoglobin) in T2DM was linked to vascular complications such as IHD and stroke. Hypertension was prevalent in 79.3% of the population. Stage 2 hypertension was more prevalent in all age groups. It was also noted that common genotypes in the Pakistani population are 3/3, 4/4, 2/3, and 3/4. The frequency of genotypes 3/4 and 2/3 is highest in diabetics with stroke. Genotype 3/3 is present frequently in diabetics with IHD/stroke and patients with both these complications. However, genotype 4/4 is most frequently found in diabetics with IHD. Conclusions: It is concluded that BMI, hypertension, hyperglycemia, atherosclerosis, and dyslipidemia are linked with cardiovascular complications of type 2 diabetes. Apolipoprotein E gene polymorphism is associated with cardiovascular disease in patients with diabetes by affecting the lipid profile.
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Apolipoproteínas E , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/complicaciones , Pakistán/epidemiología , Masculino , Femenino , Apolipoproteínas E/genética , Persona de Mediana Edad , Enfermedades Cardiovasculares/genética , Adulto , Polimorfismo Genético , Anciano , Factores de Riesgo , Dislipidemias/genética , Dislipidemias/complicaciones , Genotipo , Accidente Cerebrovascular/genética , Accidente Cerebrovascular/complicacionesRESUMEN
Phosphiranes are weak Lewis bases reacting with only a limited number of electrophiles to produce the corresponding phosphiranium ions. These salts are recognized for their propensity to undergo reactions with oxygen pronucleophiles at the phosphorus site, leading to the formation of phosphine oxide adducts. Building on a thorough mechanistic understanding, we have developed an unprecedented approach that enables the selective reaction of carboxylic acids, and other nucleophiles, at the carbon site of phosphiranes. This method involves the photochemical generation of highly reactive carbenes, which react with 1-mesitylphosphirane to yield ylides. The latter undergoes a stepwise reaction with carboxylic acids, resulting in the production of the desired phosphines. In addition to DFT calculations, we have successfully isolated and fully characterized the key intermediates involved in the reaction.
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Antibiotic resistant bacteria are immune to most antibiotics and are therefore very difficult to treat and in most cases lead to death. As such there is a pressing need for alternative and more efficient antibacterial drugs which can target these drug-resistant strains as well. The objective of this research work was to investigate the antibacterial properties of Thymus linearis essential oil (EO) against multiple disease-causing bacterial pathogens. Additionally, the study aimed to examine the molecular docking and molecular dynamic (MD) simulations of the primary components of the EO with the essential bacterial proteins and enzymes. Gas chromatography-mass spectrometry was employed to analyse the chemical composition of Thymus linearis EO. The initial screening for antibacterial properties involved the use of disc diffusion and microdilution techniques. Molecular docking studies were conducted utilising Autodock Vina. The outcomes were subsequently visualised through BIOVIA Discovery Studio. MD simulations were conducted using iMODS, an internet-based platform designed for MD simulations. The essential oil (EO) was found to contain 26 components, with thymol, carvacrol, p-cymene, and γ-terpinene being the primary constituents. The study findings revealed that Thymus linearis EO demonstrated antibacterial effects that were dependent on both the dose and time. The results of molecular docking studies revealed that the primary constituents of the EO, namely thymol, carvacrol, and p-cymene, exhibited robust interactions with the active site of the bacterial DNA gyrase enzyme. This finding provides an explanation for the antibacterial mechanism of the EO. The results indicate that Thymus linearis EO possesses potent antibacterial properties against the MDR microorganisms. Molecular docking analyses revealed that the essential oil's primary components interact with the amino acid residues of the DNA-Gyrase B enzyme, resulting in a favourable docking score.
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Aceites Volátiles , Thymus (Planta) , Aceites Volátiles/farmacología , Aceites Volátiles/química , Timol , Simulación del Acoplamiento Molecular , Girasa de ADN , Novobiocina , Antibacterianos/farmacologíaRESUMEN
In this work, we utilized electrospinning to develop advanced composite membranes of polyvinyl chloride (PVC) loaded with postmetalated metal-organic frameworks (MOFs), specifically UiO-66(COOH)2-Ag and ZIF-8-Ag. This innovative technique led to the creation of highly stable PVC/MOFs-Ag membrane composites, which were thoroughly characterized using various analytical techniques, including scanning electron microscopy, powder X-ray diffraction, thermogravimetric analysis, X-ray photoelectron spectroscopy, porosity analysis, and water contact angle measurement. The results verified the successful integration of MOF crystals within the nanofibrous PVC membranes. The obtained composites exhibited larger fiber diameters for 5 and 10% MOF loadings and a smaller diameter for 20% loading. Additionally, they displayed greater average pore sizes than traditional PVC membranes across most MOF loading percentages. Furthermore, we examined the antibacterial properties of the fabricated membranes at different MOFs-Ag loadings. The findings revealed that the membranes demonstrated significant antibacterial activity up to 95% against both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria as the MOFs-Ag loading increased, even when maintaining a constant silver concentration. This indicates a contact-based inhibition mechanism. The outcomes of this study have crucial implications for the development of novel, stable, and highly effective antibacterial materials, which could serve as superior alternatives for face masks and be integrated into materials requiring regular decontamination, as well as potential water filtration systems.
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Fluorescent nanoparticles used in biomedical applications should be stable in their colloidal form in aqueous media and possess a high quantum yield (QY). We report ultrasmall Ln2O3 (Ln = Eu, Tb, or Dy) nanoparticle colloids with high QYs in aqueous media. The nanoparticles are grafted with hydrophilic and biocompatible poly(acrylic acid) (PAA) to ensure colloidal stability and biocompatibility and with organic photosensitizer 2,6-pyridinedicarboxylic acid (PDA) for achieving a high QY. The PAA/PDA-Ln2O3 nanoparticle colloids were nearly monodispersed and ultrasmall (particle diameter: â¼2 nm). They exhibited excellent colloidal stability with no precipitation after synthesis (>1.5 years) in aqueous media, very low cellular toxicity, and very high absolute QYs of 87.6, 73.6, and 2.8% for Ln = Eu, Tb, and Dy, respectively. These QYs are the highest reported so far for lanthanides in aqueous media. Therefore, the results suggest their high potential as sensitive optical or imaging probes in biomedical applications.
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Cell stress transcribing genes provide a diverse platform of molecular mediators that vary in response to toxicity. Common drug-induced liver injury (DILI) biomarkers are usually expressed in mild toxicity and limited to confirming it rather than categorizing its intensity. Thus, new parametric biomarkers are needed to be explored. Classifying the toxicological response based on the dose-level and severity of stimuli will aid in the evaluation and approach against drug exposure. The present research explored the involvement of gene expression of potential biomarkers as a severity-specific hallmark in different acetaminophen (APAP)-induced hepatotoxicity levels in C57BL/6 mice. The differentially expressed genes were annotated and analyzed using bioinformatics tools to predict canonical pathways altered by DILI. The results revealed alteration in genes encoding for antioxidant enhancement; Slc7a11, bile efflux; MDR4, fatty acid metabolism and transcriptional factors namely Srebf1 and Pparα. Potential APAP toxicity biomarkers included Adh1 and thrombin, and other DNA damage and stress chaperones which were changed at least fourfold between control and the three tested severity models. The current investigation demonstrates a dose-mediated association of several hallmark genes in APAP-induced liver damage and addressed the involvement of uncommonly studied molecular responses. Such biomarkers can be further developed into predictive models, translated for risk assessment against drug exposure and guide in building theragnostic targets.
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Acetaminofén , Enfermedad Hepática Inducida por Sustancias y Drogas , Ratones , Animales , Acetaminofén/toxicidad , PPAR alfa/genética , PPAR alfa/metabolismo , Alcohol Deshidrogenasa/metabolismo , Trombina/metabolismo , Ratones Endogámicos C57BL , Hígado/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/genética , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Biomarcadores/metabolismo , Daño del ADN , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismoRESUMEN
Carnosine is beta-alanyl histidine, a dipeptide, endogenously produced in our body by the carnosine synthase enzyme. It is an antioxidant, thus protecting from the deleterious effect of advanced glycation end products (AGEs). Similarly, aminoguanidine (AG) also prevents AGEs formation by scavenging free radicals such as reactive oxygen species (ROS)/reactive carbonyl species (RCS). This study used experimental and computational techniques to perform a comparative analysis of carnosine and AG and their inhibiting properties against glycated human serum albumin (HSA). Fructose-mediated glycation of albumin produced fluorescent structures, such as pentosidine and malondialdehyde. These AGEs were significantly reduced by carnosine and AG. At 20 mM, carnosine and AG quenches pentosidine fluorescence by 66% and 83%, respectively. A similar inhibitory effect was observed for malondialdehyde. Protein hydrophobicity and tryptophan fluorescence were restored in the presence of carnosine and AG. Aminoguanidine decreased fibrillation in HSA, while carnosine did not significantly affect aggregation/fibrillation. In addition, molecular docking study observed binding scores of -5.90 kcal/mol and -2.59 kcal/mol by HSA-aminoguanidine and HSA-carnosine complex, respectively. Aminoguanidine forms one conventional hydrogen bond with ARG A:10 and a salt bridge with ASP A:13, ASP A:259, ASP A:255, and ASP A:256 from the amine group. Similarly, carnosine forms only hydrogen bonds with GLU A:501 and GLN A:508 from the amine and hydroxy group. The root mean square deviation (RMSD) calculated from simulation studies was 1 nm upto 70 ns for the HSA-aminoguanidine complex and the spectrum of HSA-carnosine was significantly deviated and not stabilized. The superior inhibitory activity of aminoguanidine could be due to additional salt bridge bonding with albumin. Conclusively, aminoguanidine can be the better treatment choice for diabetes-associated neurological diseases.
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Diabetic nephropathy (DN) is a severe complication of diabetes that increases mortality worldwide. Long non-coding RNAs (lncRNAs) have been investigated in DN, but the precise molecular mechanism is unclear. The research aimed to study the role of lncRNA NEAT1 in DN using an in vitro model, with the goal of uncovering its potential function and molecular mechanism in the development of DN. High glucose was applied to HEK 293 cells in order to create the DN model. The expression levels of NEAT1, miR-204, and SOX4 were assessed using RT-qPCR, along with the mRNA expression of EMT-related biomarkers and fibrosis markers such as α-SMA, E-cadherin, Vimentin, Fibronectin, and Col IV in HEK 293 cells. The interaction between NEAT1, miR-204, and SOX4 was predicted using Starbase 2.0 and confirmed through dual luciferase reporter assay. In HEK 293 cells treated with high glucose, NEAT1, and SOX4 expression were down-regulated, while miR-204 expression increased in a concentration-dependent manner. NEAT1 activation in HEK 293 cells prevented high glucose-induced fibrogenesis and EMT. NEAT1 directly targeted miR-204, and its inhibitory effects on EMT and fibrogenesis were restored by miR-204 overexpression. NEAT1 also regulated high glucose-induced EMT and fibrogenesis through its influence on miR-204 and SOX4. In conclusion, the miR-204/SOX4 axis is a prospective therapeutic target for the treatment of DN since lncRNA NEAT1 inhibited high glucose-induced EMT and fibrogenesis by controlling it in DN.
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Nefropatías Diabéticas , MicroARNs , ARN Largo no Codificante , Factores de Transcripción SOXC , Humanos , Nefropatías Diabéticas/genética , Nefropatías Diabéticas/metabolismo , Glucosa/toxicidad , Células HEK293 , Riñón/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Factores de Transcripción SOXC/genéticaRESUMEN
Cochliobolus hawaiiensis Alcorn Assiut University Mycological Centre 8606 was chosen from the screened 20 fungal species as the potent producer of fibrinolytic enzyme on skimmed-milk agar plates. The greatest enzyme yield was attained when the submerged fermentation (SmF) conditions were optimized, and it was around (39.7 U/mg protein). Moreover, upon optimization of fibrinolytic enzyme production under solid-state fermentation (SSF), the maximum productivity of fibrinolytic enzyme was greatly increased recorded a bout (405 U/mg protein) on sugarcane bagasse, incubation period of 5 days, moisture level of 100%, initial pH of salt basal medium 7.8, incubation temperature at 35°C, and supplementation of the salt basal medium with corn steep liquor (80ï¼ , v/v). The yield of fibrinolytic enzyme by C. hawaiiensis under SSF was higher than that of SmF with about 10.20-fold. The purification procedures of fibrinolytic enzyme by ammonium sulfate (70%), gel filtration, and ion-exchange columns chromatography caused a great increase in its specific activity to 2581.6 U/mg protein with an overall yield of 55.89%, 6.37 purification fold and molecular weight of 35 kDa. Maximal activity was recorded at pH 7 and 37°C. Significant pH stability was recorded at pH 6.6-7.2, and thermal stability was recorded at 33-41°C. The enzyme showed the highest affinity toward fibrin, with Vmax of 240 U/mL and an apparent Km value of 47.61 mmol. Mg2+ and Ca2+ moderately induced fibrinolytic activity, whereas Cu2+ and Zn2+ greatly suppressed the enzyme activity. The produced enzyme is categorized as serine protease and non-metalloprotease. The purified fibrinolytic enzyme showed efficient thrombolytic and antiplatelet aggregation activities by completely prevention and dissolution of the blood clot which confirmed by microscopic examination and amelioration of blood coagulation assays. These findings suggested that the produced fibrinolytic enzyme is a promising agent in management of blood coagulation disorders.
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Celulosa , Saccharum , Humanos , Celulosa/metabolismo , Fermentación , Concentración de Iones de Hidrógeno , Saccharum/metabolismo , Fibrinolíticos/farmacología , Fibrinolíticos/química , Fibrinolíticos/metabolismo , Temperatura , Peso MolecularRESUMEN
In our continued efforts to find potential chemotherapeutics active against drug-resistant (DR) Mycobacterium tuberculosis (Mtb), causative agent of Tuberculosis (TB) and to curb the current burdensome treatment regimen, herein we describe the synthesis and biological evaluation of urea and thiourea variants of 5-phenyl-3-isoxazolecarboxylic acid methyl esters as promising anti-TB agent. Majority of the tested compounds displayed potent in vitro activity not only against drug-susceptible (DS) Mtb H37Rv but also against drug-resistant (DR) Mtb. Cell viability test against Vero cells deemed these compounds devoid of significant toxicity. 3,4-Dichlorophenyl derivative (MIC 0.25 µg/mL) and 4-chlorophenyl congener (MIC 1 µg/mL) among urea and thiourea libraries respectively exhibited optimum potency. Lead optimization resulted in the identification of 1,4-linked analogue of 3,4-dichlorophenyl urea derivative demonstrating improved selectivity. Further, in silico study complemented with previously proposed prodrug like attributes of isoxazole esters. Taken together, this molecular hybridization approach presents a new chemotype having potential to be translated into an alternate anti-Mtb agent.
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Antituberculosos , Mycobacterium tuberculosis , Animales , Chlorocebus aethiops , Antituberculosos/farmacología , Urea/farmacología , Células Vero , Relación Estructura-Actividad , Ácidos Carboxílicos/farmacología , Ésteres/farmacología , Tiourea/farmacología , Isoxazoles/farmacología , Pruebas de Sensibilidad MicrobianaRESUMEN
Objective. Adipose tissue is considered to be an endocrine organ that secretes bioactive substances known as adipokines that contribute to the pathophysiology of metabolic and coronary diseases related to obesity. In this study, various novel biomarkers, such as inflammatory markers that are pro-inflammatory (visfatin) and anti-inflammatory (omentin-1), as prognostic indicators for people with coronary artery disease (CAD) were investigated. Methods. In this study, 30 diabetic patients with CAD, 30 diabetic patients without CAD, and 30 healthy control counterparts were included. Serum omentin and visfatin concentrations were evaluated by solid-phase enzyme linked immunosorbent assay (ELISA) kit. Patients with established diagnosis of CAD based on angiography, ECG, and elevated cardiac marker level were included into the study. Patients with cardioembolic stroke, cerebral venous sinus thrombosis, CNS vasculitis, and hemorrhage due to trauma, tumor, vascular malformation, and coagulopathy were excluded. Results. The serum omentin-1 levels were significantly higher in the healthy controls in comparison with the diabetic group (p<0.0001) and serum visfatin levels were significantly higher in the diabetic group in comparison with the healthy controls (p<0.0001). The serum omentin levels were significantly higher in the diabetic group in comparison with the cardio-diabetic group (p<0.0001) and serum visfatin levels were significantly higher in the cardio-diabetic group in comparison with the diabetic group (p<0.0001). The serum omentin-1 showed negative correlation with the serum visfatin in the cardio-diabetic group. Conclusion. The adipokines, such as omentin and visfatin, may be good therapeutic candidates in preventing or ameliorating CAD.
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Enfermedad de la Arteria Coronaria , Diabetes Mellitus , Humanos , Adipoquinas/metabolismo , Nicotinamida Fosforribosiltransferasa , Citocinas , Tejido Adiposo/metabolismoRESUMEN
BACKGROUND: Knowing what to eat and realizing the significance of healthful eating habits are among the important steps to promoting eating behavior. The current study aims to assess the nutrition knowledge (NK) among a convenient sample in four different countries, determine the association between different demographic factors and NK, and investigate the need for future interventions on nutrition in the four selected countries. METHODS: A cross-sectional multi-national survey study among a convenient sample of 8,191 subjects from Egypt, Syria, Saudi Arabia, and Jordan who undertook surveys between January 2019 and January 2020. A pre-tested interview questionnaire was utilized for data collection from study participants. It included three sections: i) Sociodemographic characteristics:. ii). Section two included twenty-one questions related to NK.. iii). Section three included one question about NK sources. RESULTS: About three-quarters showed inadequate nutrition knowledge (73.1%). Youth (15-24 yrs.) were more dependent on social media, with 87% using it as a primary source of NK, while adults (≥ 25 yrs.) demonstrated that 43% of them used social media. In contrast, TV was more prominent among them, with participants' characteristics such as living with parents, body mass index, and country of residence showing no association with NK. However, female sex, education, and reading nutrition articles are significantly correlated with adequate knowledge (p < 0.001). Significant predictors of satisfactory knowledge were age, sex, education, living with parents, and reading nutrition articles. CONCLUSION: The study revealed low levels of NK indicating an urgent need to implement educational programs to promote nutrition knowledge. As NK is a modifiable determinant of diet intake and can positively impact the need for developing strategies in counselling and raising awareness among the general population to improve their health status.